Role of hydrophobic effects in mechanistic QSAR

To extend the successful application of Hammett equations, previously used to predict equilibrium and rates of physico-chemical reactions with electro nic and steric parameters, to the realm of biology and biochemistry, a para meter that measures hydrophobicity is required. The partition coefficient o f a solute between octanol and water, expressed in log terms to put it on t he same free-energy basis as the classic Hammett parameters, has been shown to be widely applicable. It is directly involved in passive transport thro ugh membranes, in binding to proteins, and in specific binding at active si tes in enzymes. Methods of calculating logP(octanol) that reflect the solva tion forces involved, can be useful in elucidating unusual solute conformat ions that may be preferred in a non-polar environment.